Clinical trials continue to be a cornerstone to the effort to advance care and improve outcomes for cancer patients. ECOG and ACRIN collectively have over 65 years of experience conducting high impact clinical trials that have helped shaped clinical practice. In response to the National Clinical Trials Network (NCTN) initiative, ECOG and ACRIN have merged their complementary scientific programs to form the ECOG-ACRIN Cancer Research Group (E-A). We propose a program focused on the efficient development and implementation of practice-changing science along the cancer care continuum from early detection through treatment of advanced disease. We take advantage of combined expertise in imaging, cancer biology and therapy within our scientific organization, working closely with the biostatistics and data management center at the Dana Farber Cancer Institute and Brown University, to propose a portfolio of treatment and advance imaging trials that recognize the importance of biomarkers to identify appropriate patient subgroups for precisely targeted intervention. The E-A biorepositories, image database and associated translational science centers will leverage the data collected in the context of trials to perform correlative science studies that advance our understanding of cancer biology and treatment effect. We continue to seamlessly integrate with Cancer Center and SPORE research programs to create an interface for translating NCI-supported science into clinical trials and to attract junior investigators into the NCTN. We propose to continue collaborating across the NCTN, contributing high quality trials, leadership in advance imaging, joint trial development and important NCTN operational infrastructure. E-A will leverage unique clinical informatics expertise to contribute a data warehouse of annotated images and specimens, laboratory analytics and clinical data to foster scientific discovery. E-A will contribute an accrual network of 37 main member institutions, 200 affiliates, 36 CCOPs and minority-based CCOPs that have accrued 33750 patients to clinical trials over the last 6 years. E-A is positioned to make unique contributions to the NCTN, working to translate NCI-supported science into improved outcomes for cancer patients.